title: Expression of nuclear-encoded genes involved in mitochondrial biogenesis and dynamics in experimentally denervated muscle.
abstract: The abundance, morphology, and functional properties of mitochondria become altered in response to denervation. To gain insight into the regulation of this process, mitochondrial enzyme activities and gene expression involved in mitochondrial biogenesis and dynamics in mouse gastrocnemius muscle was investigated. Sciatic nerve transactions were performed on mice, and then gastrocnemius muscles were isolated at days 5 and 30 after surgery. Muscle weight was decreased significantly by 15% and 62% at days 5 and 30 after surgery, respectively. The activity of citrate synthase, a marker of oxidative enzyme, was reduced significantly by 31% and 53% at days 5 and 30, respectively. Enzyme histochemical analysis revealed that subsarcolemmal mitochondria were largely lost than intermyofibrillar mitochondria at day 5, and this trend was further progressed at day 30 after surgery. Expression levels of peroxisome proliferator-activated receptor, γ coactivator 1 (PGC-1)α, estrogen-related receptor α (ERRα), and mitofusin 2 were down-regulated throughout the experimental period, whereas those of PGC-1β, PRC, nuclear respiratory factor (NRF)-1, NRF-2, TFAM, and Lon protease were down-regulated at day 30 after surgery. These results suggest that PGC-1α, ERRα, and mitofusin 2 may be important factors in the process of denervation-induced mitochondrial adaptation. In addition, other PGC-1 family of transcriptional coactivators and DNA binding transcription factors may also contribute to mitochondrial adaptation after early response to denervation.
authors.affiliation: Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan. wagatsuma1969@yahoo.co.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Wagatsuma
authors.forename: Naoki
authors.initials: N
authors.lastname: Kotake
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Mabuchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D057075:Enzyme Assays; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008931:Mitochondria, Muscle / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D053142:Mitochondrial Size; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism* / Q000473:pathology; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism; D009929:Organ Size; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D049070:Protease La / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D004268:DNA-Binding Proteins; D051268:GA-Binding Protein Transcription Factor; D020558:GTP Phosphohydrolases; D006609:High Mobility Group Proteins; D024101:Mitochondrial Proteins; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D049070:Protease La; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C561064:FIS1 protein, mouse; C495634:Nrf1 protein, mouse; C485290:Ppargc1a protein, mouse; C081930:Tfam protein, mouse; C484072:mtSSB protein, mouse; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; C488751:Mfn2 protein, mouse